Short telomere length is associated with impaired cognitive performance in European ancestry cohorts.

The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N=17 052; mean age=59.2±8.8 years) provided results for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL including seven known genetic variants for TL was calculated, and used in associations with cognitive traits as outcomes in all cohorts. Observational analyses showed that longer telomeres were associated with better scores on DSST (ß=0.051 per s.d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P=0.0002), and MMSE (ß=0.025; 95% CI: 0.002, 0.047; P=0.03), and faster STROOP (ß=-0.053; 95% CI: -0.087, -0.018; P=0.003). Effects for DSST were stronger in APOE ɛ4 non-carriers (ß=0.081; 95% CI: 0.045, 0.117; P=1.0 × 10-5), whereas carriers performed better in STROOP (ß=-0.074; 95% CI: -0.140, -0.009; P=0.03). Causal associations were found for STROOP only (ß=-0.598 per s.d.-increase of TL; 95% CI: -1.125, -0.072; P=0.026), with a larger effect in ɛ4-carriers (ß=-0.699; 95% CI: -1.330, -0.069; P=0.03). Two-sample replication analyses using CHARGE summary statistics showed causal effects between TL and general cognitive function and DSST, but not with STROOP. In conclusion, we suggest causal effects from longer TL on better cognitive performance, where APOE ɛ4-carriers might be at differential risk.

Validity of a single question to assess habitual physical activity of community-dwelling older people.

The aim is to determine concurrent validity of a single self-report habitual physical activity (PA) question against accelerometer-based PA and mobility variables, and corresponding changes in self-reported PA and mobility. Cross-sectional and longitudinal data of the "Life-space mobility in old age" (LISPE) cohort and its substudy on PA were utilized. At baseline, 848 community-dwelling, 75- to 90-year-old people living independently in central Finland participated in home-based interviews. One and 2 years later, 816 and 761 of them were reassessed by phone, respectively. Tri-axial accelerometer data over 7 days were collected following the baseline assessments in a subsample of 174. Self-reported habitual PA was assessed based on intensity and duration using a single question with seven response options (range: mostly resting to competitive sports). Mobility variables were as follows: life-space mobility, walking difficulty over 500 m, and short physical performance battery. Statistically significant correlations were found between self-reported habitual PA and mobility (Spearman correlation coefficient Rs = 0.40-0.61) and accelerometer-based PA variables [step counts (Rs = 0.49), time in moderate (Rs = 0.49) and low intensity (Rs = 0.40) PA, and time in sedentary behavior (Rs = -0.28)]. A decline in self-reported habitual PA over time was associated with 5-10p decline in life-space mobility (PA improvement with 0-3p increase) and with developing a higher degree of walking difficulty (in 35-44% of participants). In conclusion, based on these results, the self-report question to assess habitual PA is valid and responsive to change and thus useful for epidemiological research in community-dwelling older people, also in follow-up studies.

The association between objectively measured physical activity and life-space mobility among older people.

The purpose of this cross-sectional study was to investigate the association between objectively measured physical activity and life-space mobility in community-dwelling older people. Life-space refers to the spatial area a person purposefully moves through in daily life (bedroom, home, yard, neighborhood, town, and beyond) and life-space mobility to the frequency of travel and the help needed when moving through different life-space areas. The study population comprised community-living 75- to 90-year-old people {n = 174; median age 79.7 [interquartile range (IQR) 7.1]}, participating in the accelerometer substudy of Life-Space Mobility in Old Age (LISPE) project. Step counts and activity time were measured by an accelerometer (Hookie "AM20 Activity Meter") for 7 days. Life-space mobility was assessed with Life-Space Assessment (LSA) questionnaire. Altogether, 16% had a life-space area restricted to the neighborhood when moving independently. Participants with a restricted life space were less physically active and about 70% of them had exceptionally low values in daily step counts (≤ 615 steps) and moderate activity time (≤ 6.8 min). Higher step counts and activity time correlated positively with life-space mobility. Prospective studies are needed to clarify the temporal order of low physical activity level and restriction in life-space mobility.

The interaction of blood flow, insulin, and bradykinin in regulating glucose uptake in lower-body adipose tissue in lean and obese subjects.

CONTEXT: Impaired adipose tissue (AT) blood flow has been implicated in the pathogenesis of insulin resistance in obesity. Insulin and bradykinin are meal-stimulated promoters of AT blood flow and glucose metabolism. OBJECTIVE: We tested whether blood flow regulates glucose metabolism in AT, insulin and bradykinin exert additive effects on AT blood flow and metabolism, and any of these actions explains the insulin resistance observed in obese individuals. DESIGN: Perfusion and glucose metabolism in the AT of the thighs were studied by positron emission tomography and H(2)(15)O (flow tracer) and (18)F-2-fluoro-2-deoxyglucose. Study I included five subjects in whom positron emission tomography imaging was performed in the fasting state during intraarterial infusion of bradykinin in the left leg; the right leg served as a control. Study II included seven lean and eight obese subjects in whom the imaging protocol was performed during euglycemic hyperinsulinemia. RESULTS: Bradykinin alone doubled fasting AT blood flow without modifying glucose uptake. Hyperinsulinemia increased AT blood flow (P ≤ 0.05) similarly in lean and obese individuals. In the lean group, bradykinin increased insulin-mediated AT glucose uptake from 8.6 ± 1.6 to 12.3 ± 2.4 µmol/min · kg (P = 0.038). In the obese group, AT glucose uptake was impaired (5.0 ± 1.0 µmol/min · kg, P = 0.05 vs. the lean group), and bradykinin did not exert any metabolic action (6.0 ± 0.8 µmol/min · kg, P = 0.01 vs. the lean group). CONCLUSION: AT blood flow is not an independent regulator of AT glucose metabolism. Insulin is a potent stimulator of AT blood flow, and bradykinin potentiates the hemodynamic and metabolic actions of insulin in lean but not in obese individuals.

Self-reported preclinical mobility limitation and fall history as predictors of future falls in older women: prospective cohort study.

UNLABELLED: We studied if self-reported preclinical mobility limitation, described as modification of task performance without perception of difficulty, predicts future falls in older women with and without fall history. Our results suggest that combined measure of self-reported preclinical mobility limitation and fall history may offer one possibility for inexpensive fall-risk evaluation in clinical practice. INTRODUCTION: We studied if self-reported preclinical mobility limitation predicts future falls in older women with and without fall history. METHODS: The study population consisted of 428 community-living 63-76-year-old women. At baseline, those who expressed no difficulty walking 2 km but reported that it took longer than before or that they did it less often were categorized as having preclinical mobility limitation. Those reporting difficulty in 2-km walk were categorized as having manifest mobility limitation. Fall history was recalled for previous 12 months and dichotomized. The incidence of future falls over 12 months was followed up with fall calendars. RESULTS: During the fall follow-up, a total of 440 falls were reported by 201 participants. Among those with fall history, women with preclinical mobility limitation had almost 4-fold (incidence rate ratios 3.77; 95% CI 1.02-13.92) and those with manifest mobility limitation almost 15-fold (14.66; 2.72-79.00) adjusted risk for future falls compared to those with no mobility limitation and no previous falls. Among women without fall history, preclinical and manifest mobility limitation did not predict future falls nor did fall history without mobility limitation. CONCLUSIONS: Already, early signs of mobility decline with history of falls increase the risk of further falls and should be considered as indications for fall prevention interventions.

Non-invasive estimation of hepatic glucose uptake from [18F]FDG PET images using tissue-derived input functions.

PURPOSE: The liver is perfused through the portal vein and hepatic artery. Quantification of hepatic glucose uptake (HGU) using PET requires the use of an input function for both the hepatic artery and portal vein. The former can be generally obtained invasively, but blood withdrawal from the portal vein is not practical in humans. The aim of this study was to develop and validate a new technique to obtain quantitative HGU by estimating the input function from PET images. METHODS: Normal pigs (n = 12) were studied with [18F]FDG PET, in which arterial and portal blood time-activity curves (TAC) were determined invasively to serve as reference measurements. The present technique consisted of two characteristics, i.e. using a model input function and simultaneously fitting multiple liver tissue TACs from images by minimizing the residual sum of square between the tissue TACs and fitted curves. The input function was obtained from the parameters determined from the fitting. The HGU values were computed by the estimated and measured input functions and compared between the methods. RESULTS: The estimated input functions were well reproduced. The HGU values, ranging from 0.005 to 0.02 ml/min per ml, were not significantly different between the two methods (r = 0.95, p < 0.001). A Bland-Altman plot demonstrated a small overestimation by the image-derived method with a bias of 0.00052 ml/min per g for HGU. CONCLUSION: The results presented demonstrate that the input function can be estimated directly from the PET image, supporting the fully non-invasive assessment of liver glucose metabolism in human studies.

On-call stress among Finnish anaesthetists.

We investigated on-call stress and its consequences among anaesthetists. A questionnaire was sent to all working Finnish anaesthetists (n = 550), with a response rate of 60%. Four categories of on-call workload and a sum variable of stress symptoms were formed. The anaesthetists had the greatest on-call workload among Finnish physicians. In our sample, 68% felt stressed during the study. The most important causes of stress were work and combining work with family. The study showed a positive correlation between stress symptoms and on-call workload (p = 0.009). Moderate burnout was present in 18%vs 45% (p = 0.008) and exhaustion in 32% and 68% (p = 0.015), in the lowest vs highest workload category, respectively. The symptoms were significantly associated with stress, gender, perceived sleep deprivation, suicidal tendencies and sick leave. Being frequently on call correlates with severe stress symptoms and these symptoms are associated with sick leave.

Medicine and the humanities--theoretical and methodological issues.

Engel's biopsychosocial model, Cassell's promotion of the concept "person" in medical thinking and Pellegrino's and Thomasma's philosophy of medicine are attempts to widen current biomedical theory of disease and to approach medicine as a form of human activity in pursuit of healing. To develop this approach further we would like to propose activity theory as a possible means for understanding the nature of medical practice. By "activity theory" we refer to developments which have evolved from Vygotsky's research on socially mediated mental functions and processes. Analysing medicine as activity enforces the joint consideration of target and subject: who is doing what to whom. This requires the use of historical, linguistic, anthropological, and semiotic tools. Therefore, if we analyse medicine as an activity, humanities are both theoretically and methodologically "inbound" (or internal) to the analysis itself. On the other hand, literature studies or anthropological writings provide material for analysing the various forms of medical practices.

Reconstruction of the anterior cruciate ligament with carbon fibres: unsatisfactory results after 8 years.

A total of 37 patients were operated on for anterior cruciate ligament (ACL) insufficiency between 1980 and 1989 using two types of carbon fibre ligament substitutes. The average age of the population was 23.6 years. The carbon fibre prostheses were covered with either a strip of medial joint capsule or lyophilized dura. Follow-up averaged 8.1 years (range 4-13 years), most of the operations being done from 1983 to 1985. Evaluation included a questionnaire, physical examination, Lysholm scoring, radiographs and cruciometer testing. The operated ACLs were looser than those in the contralateral healthy knees. The Lysholm scoring system gave acceptable results (excellent and good) in 43.5%, fair in 31.4% and poor in 24.1% of cases. Acceptable results provided better stability and muscle strength. During the follow-up there was an evident deterioration in stability as well as in Lysholm score. The results between the two types of ligaments did not become statistically different. Osteoarthrosis increased in all the knees examined radiographically (28/37). The results indicate that the ACL reconstructions using these types of carbon fibre prostheses lead to unacceptable results in the long-term follow-up.

Frostbite of the face and ears: epidemiological study of risk factors in Finnish conscripts.

OBJECTIVE: To determine the incidence of and the risk factors for local cold injuries of the face and ears in peacetime military service. DESIGN: Prospective, controlled epidemiological study using a questionnaire. SETTING: Finnish defence forces, 1976-89. SUBJECTS: 913 young male conscripts with local frostbite of the head that needed medical attention and 2478 uninjured control conscripts. MAIN OUTCOME MEASURES: Type of activity, clothing, and other risk factors at the time of cold injury. Odds ratios were used to calculate risk. Controls were handled as one group. RESULTS: The mean annual incidence of frostbite was 1.8 per 1000 conscripts. Frostbite of the ear was most common (533 conscripts (58%)), followed by frostbite of the nose (197 (22%)) and of the cheeks and other regions of the face (183 (20%)). Most conscripts (803 (88%)) had mild or superficial frostbite. Risk factors included not wearing a hat with earflaps (odds ratio 18.5 for frostbite of the ear); not wearing a scarf (odds ratio 2.1 and 3.8 for frostbite of the ear and cheeks respectively); using protective ointments (odds ratio 3.3, 4.5, and 5.6 for frostbite of the cheeks, ear, and nose respectively); being extremely sensitive to cold and having hands and feet that sweat profusely (odds ratio 3.5 for frostbite of the nose); and being transported in the open or in open vehicles under windy conditions (odds ratio 2.2 for frostbite of the cheek). CONCLUSIONS: Wearing warm clothing, including a scarf and a hat with earflaps, helps to prevent frostbite. Each person's sensitivity to cold may also be important. The routine use of protective ointments should not be recommended.

Neuropsychologic and cardiovascular effects of clemastine fumarate under pressure.

Allergic rhinitis and mild respiratory infections have been widely accepted as temporary contraindications for fitness to dive. Nonetheless, several sport and professional divers use antihistamines to ease ear, nose, and throat (ENT) problems, especially for opening tubal ostium. Some divers know they are unfit to dive, but for a variety of reasons (e.g., money or short holiday) they try to clear their ears. Thus, the use of antihistaminic drugs (like clemastine fumarate) is common during diving. This double-blind, crossover study indicates that this special antihistamine does not increase the sedative effects of nitrogen narcosis, nor does it increase the level of cardiac arrhythmias. Liberal use of antihistamines while diving cannot be recommended because of possible complications connected with different preparations and the temporary limitations they impose on the diver.

Cardiovascular functional disorder and stress among patients having neck-shoulder symptoms.

OBJECTIVES: To investigate if autonomic nervous system function, reflected in cardiovascular variables, among patients with neck-shoulder symptoms (tension neck group (T)) differed from that in a symptom free control group (C), and to establish its relation with pain and psychological stress. METHODS: Twelve women with tension neck and nine controls in secretarial jobs were studied. They underwent an orthostatic test, deep breathing test, Valsalva manoeuvre, isometric handgrip test, and muscular endurance test. Pain was measured using visual analogue scales, and psychological stress by the Modified Somatic Perception Questionnaire (MSPQ). Plasma endothelin-1 (ET-1) was measured using high pressure liquid chromatography and radioimmunoassay. RESULTS: Signs of psychological stress were significantly (p < 0.001) more common in group T than in group C. Mean resting heart rate in group T (77.8 (SE 2.9) beats/min; range 64-100) was significantly greater than that in group C (63.8 (3.1) beats/min; range 52-80) (p < 0.01). In the orthostatic test, the overall changes in R-R intervals during the first 40 heart beats after standing up and during seven minutes of testing differed significantly between the groups (p < 0.001, < 0.05, respectively). The increase in diastolic blood pressure in the three minute isometric handgrip test was significantly less in group T (19.4 (3.5) mm Hg; range -5 to 35) than in group C (30 (3.4) mm Hg; range 15-50) (p < 0.05). The MSPQ score in the study group (n = 21) correlated positively with resting heart rate (r = 0.462, p < 0.05) and negatively with increase in diastolic blood pressure (r = -0.514, p < 0.05). Plasma concentrations of ET-1 did not differ between the groups. CONCLUSION: Increased sympathetic activity was found among patients having neck-shoulder symptoms. Local mechanisms may have influenced the cardiovascular changes observed during isometric testing in these patients.

Cardiovascular functional disorder and distress among patients with thoracic outlet syndrome.

Cardiovascular functional stability of 11 women with thoracic outlet syndrome (TOS; mean age 34.5) and nine female controls (mean age 35.1) was studied using an orthostatic test, a deep breathing test, Valsalva manoeuvre and hand-grip test. The heart rate at rest was significantly higher in TOS patients. The TOS group showed significant accentuation in T wave vacillation in the orthostatic test. The rise in diastolic blood pressure of the TOS group during a hand-grip test was significantly less than that of the control group. TOS patients experienced significantly more distress according to the modified somatic perception questionnaire (MSPQ) than the control group. Pain was correlated with the score of MSPQ, the resting heart rate and increase in diastolic blood pressure in a hand-grip test. The results suggest that TOS patients' symptoms often reflect a wider disturbance than merely anatomical compression in the thoracic outlet. It seems possible that sympathetic tone is higher in TOS patients than in controls. In addition to possible operative treatment, it may be necessary to provide psychological help, relaxation and endurance training.

Cardiovascular functional disorder in primary fibromyalgia: a noninvasive study in 17 young men.

Cardiovascular functional stability was studied in 17 young men (20-year-old conscripts) with the symptoms of primary fibromyalgia (PF). They were compared to 20 medical students of the same age. The subjects underwent an orthostatic test, deep breathing test, Valsalva maneuver, and a handgrip test. They were evaluated by an autoanamnestic questionnaire on vegetative symptoms and laboratory tests on blood chemistry. The heart rate of the PF group after 8 min of active standing was 32 +/- 15 beats/min greater than at supine rest. The corresponding figure for the controls was 23 +/- 7 beats/min (p = 0.001). Twelve conscripts with PF (71%) presented sympathicotonic cardiovascular reaction on the orthostatic test (p < 0.001). Four of these sympathicotonic conscripts and two other conscripts (total 35%) had an abnormal high index of dystonic symptoms (p = 0.01). The results suggest that young men with symptoms of PF have not only cardiovascular dystonic symptoms but also increased sympathetic nervous reactivity of the cardiovascular system.

Pleuropulmonary involvement during bromocriptine treatment.

The use of bromocriptine in the treatment of Parkinson's disease is increasing. More than 20 cases of suggested drug-induced pleuropulmonary disorders during bromocriptine therapy have been reported. We describe four male parkinsonian patients taking bromocriptine in whom pleuropulmonary abnormalities were discovered in a pulmonary hospital during a one-year period. In only one case were the roentgenographic changes reversible after withdrawal of the drug. Pleural fluid from two patients was analyzed and showed lymphocyte-predominant chronic inflammatory changes. Raised erythrocyte sedimentation rate (ESR) and C-reactive protein values decreased after cessation of bromocriptine. Lung function studies demonstrated volume restriction with normal or high CO transfer coefficient. The frequency of pleuropulmonary changes during bromocriptine therapy may be greater than assumed, and such patients may initially present with nonrespiratory symptoms. Follow-up of patients during bromocriptine treatment by ESR, C-reactive protein, and chest roentgenogram is recommended.

Inhaled budesonide influences cellular and biochemical abnormalities in pulmonary sarcoidosis.

In a randomized, double-blind study 19 patients with newly-detected pulmonary sarcoidosis were treated with either inhaled budesonide, 800 micrograms twice daily (n = 9), or placebo (n = 10) for 8-10 weeks. Before and after treatment, chest roentgenograms, lung function tests, bronchoalveolar lavage (BAL) and biochemical tests were performed. Angiotensin converting enzyme (ACE) activity and beta2-microglobulin (beta 2M) concentrations were measured in serum. The same tests, as well as albumin and hyaluronan were measured in the BAL-fluid. The total cell number in BAL-fluid, differential counts and lymphocyte subpopulations were determined (total T- and B-lymphocytes, T-helper/inducer (OKT-4) and T-suppressor/cytotoxic (OKT-8) lymphocytes). No significant changes in chest roentgenograms or lung function tests were observed during the short study time. However, a decrease in serum ACE (p less than 0.1) and beta 2 M (p less than 0.05) as well as in BAL-hyaluronan (p less than 0.01) was found in the budesonide-treated patients as well as a decrease in the percentage of BAL T-lymphocytes (p less than 0.05) and the T4/T8 ratio (p less than 0.1). No significant changes were seen in the placebo group. The findings suggest that treatment with inhaled budesonide influences biochemical and cellular findings in patients with early sarcoidosis in the same way as treatment with systemic corticosteroids. The results may also explain clinical effects seen in sarcoidosis patients treated with inhaled corticosteroids. However, further studies are required to determine the long-term clinical benefits of inhaled steroids in pulmonary sarcoidosis.

Reappearance of Hering-Breuer reflex after bilateral autotransplantation of the lungs.

In combined heart-lung transplantation the afferent nerve pathways inevitably are transsected. In previous studies with en bloc heart-lung transplantation in dogs, we found altered regulation of breathing-abolition of Hering-Breuer reflex and response to hypercapnia inhalation stimulus consisting of augmented tidal volume with no change in respiratory rate-shortly after the operation. The long-term effects of pulmonary denervation on breathing regulation were now studied in dogs after staged bilateral pulmonary autotransplantation. Mechanical and electrical activities of the respiratory muscles were recorded during spontaneous breathing and after deflation and inflation with varying volumes of air. Five months postoperatively the duration of the respiratory cycle increased 2.5 times on inflation with 600 ml of air and occlusion of the airways, compared with tenfold prolongation in intact control dogs, indicating a partial return of the Hering-Breuer reflex after the autotransplantation. The duration of the EMG bursts in respiratory muscles increased in intact dogs and in those with bilateral lung autotransplants. In impulse frequency the response to stretching was less evident after autotransplantation. The mechanism mediating reappearance of Hering-Breuer reflex warrants further study.

Effect of lung autotransplantation on breathing regulation. Studies in dogs.

The effect of autotransplantation of the left lung on respiratory regulation was studied in four dogs in pentobarbital anaesthesia. In each dog the electrical and mechanical activity of the inspiratory muscles was studied before and 4-6 weeks, 3, 6 and 12 months after the transplantation. No or very little change was found in comparisons of spontaneous respiration or response to inhalation of carbon dioxide, hypoxia or combined hypercapnia and hypoxia. When the airways were closed after inflation with varying volumes of air, the increase in number and frequency of the electromyographic impulses in the intercostal muscles and the diaphragm (compared with the preceding unobstructed breaths) was greater before than after the lung autotransplantation. The duration of the first respiratory cycle after airway closure increased progressively with the volume of inflation in intact dogs and in dogs with autotransplanted left lung, though the increase was approximately halved following autotransplantation.